11 results on '"Neely RDG"'
Search Results
2. Lipoprotein(a) and cardiovascular disease: sifting the evidence to guide future research.
- Author
-
Kamstrup PR, Neely RDG, Nissen S, Landmesser U, Haghikia A, Costa-Scharplatz M, Abbas C, and Nordestgaard BG
- Subjects
- Humans, Biomarkers blood, Risk Assessment, Risk Factors, Heart Disease Risk Factors, Biomedical Research, Evidence-Based Medicine, Lipoprotein(a) blood, Cardiovascular Diseases prevention & control, Cardiovascular Diseases blood
- Abstract
Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease including coronary heart disease, peripheral arterial disease, ischaemic stroke, and calcific aortic valve stenosis. Clinical trials of specific and potent Lp(a)-lowering drugs are currently underway. However, in clinical practice, widespread assessment of Lp(a) is still lacking despite several guideline recommendations to measure Lp(a) at least once in a lifetime in all adults to identify those at high or very high risk due to elevated levels. The present review provides an overview of key findings from observational and genetic Lp(a) studies, highlights the main challenges in observational Lp(a) studies, and proposes a minimum set of requirements to enhance the quality and harmonize the collection of Lp(a)-related data. Adherence to the recommendations set forth in the present manuscript is intended to enhance the quality of future observational Lp(a) studies, to better define thresholds for increased risk, and to better inform clinical trial design. The recommendations can also potentially assist in the interpretation and generalization of clinical trial findings, to improve care of patients with elevated Lp(a) and optimize treatment and prevention of cardiovascular disease., Competing Interests: Conflict of interest: P.R.K. reports talks and consultancies sponsored by the Physicians’ Academy for Cardiovascular Education, Silence Therapeutics, Novartis, and the PCSK9 Forum. R.D.G.N. reports consultancies and talks sponsored by Amgen, Novartis, and Pfizer. S.N. reports that the Cleveland Clinic Center for Clinical Research has received funding to perform clinical trials from AbbVie, AstraZeneca, Amgen, Arrowhead, Bristol Myers Squibb, Eli Lilly, Esperion, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, Pfizer, and Silence Therapeutics. The author receives no personal remuneration for participation in these trials. U.L. reports receiving institutional research grants from Abbott, Amgen, Bayer, and Novartis as well as lecture or consultant honoraria from Abbott, Amgen, Novartis, Sanofi, and Novo Nordisk. A.H. reports consultancies and talks sponsored by Novo Nordisk, Novartis, Bayer, and AstraZeneca. M.C.-S. and C.A. are employees of Novartis. B.G.N. reports consultancies and talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea Therapeutics, Ionis, Amgen, Kowa, Denka, Amarin, Novartis, Novo Nordisk, Silence Therapeutics, Abbott, Ultragenyx, and Esperion., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2024
- Full Text
- View/download PDF
3. Lipoprotein(a) testing in lipid clinics across the UK: Results of a national survey.
- Author
-
Ansari S, Neely RDG, Payne J, and Cegla J
- Subjects
- Humans, United Kingdom epidemiology, Surveys and Questionnaires, Middle Aged, Female, Male, Lipoprotein(a) blood, Cardiovascular Diseases blood, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology
- Abstract
Lipoprotein(a) is an independent risk factor for cardiovascular disease and its use is recommended in national and international guidelines for cardiovascular disease risk stratification. We undertook a survey to understand the availability and application of lipoprotein(a) measurement across UK lipid clinics. Fifty-three out of an estimated 200 lipid clinics (27%) provided responses. Eighty-one percent of 53 clinics had access to lipoprotein(a) measurement. Twenty-seven clinics disclosed the number of lipoprotein(a) tests ordered annually with approximately half of the clinics (52%) requesting 0-250 tests per year. Sixty percent measured lipoprotein(a) once per patient and the leading indication was a personal or family history of premature history of cardiovascular disease in those <60 years old. Sixty-three percent of clinics that provided comments with lipoprotein(a) results graded cardiovascular risk as per the HEART UK consensus statement. Sixty percent of clinics performed family cascade testing on lipoprotein(a) results ≥200 nmol/L. Lipoprotein(a) was reported in nmol/L, mg/dL, or mg/L by 48%, 24%, and 28% of responding clinics, respectively. National effort is required to provide universal access to lipoprotein(a) measurement and to harmonise the clinical application of this data., Competing Interests: Declaration of competing interest JC and RDGN have received lecture honoraria, consultancy fees, and/or research funding from Novartis., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
4. How should public health recommendations address Lp(a) measurement, a causative risk factor for cardiovascular disease (CVD)?
- Author
-
Catapano AL, Daccord M, Damato E, Humphries SE, Neely RDG, Nordestgaard BG, Pistollato M, and Steinhagen-Thiessen E
- Subjects
- Humans, Lipoprotein(a), Public Health, Risk Factors, Atherosclerosis etiology, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control
- Abstract
Background and Aims: Elevated concentrations of Lipoprotein (a) [Lp(a)] is an inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). This study aims to investigate the clinical utility for patients, and the economic benefit to healthcare systems and society of measuring Lp(a) concentrations more widely today., Methods: We conducted a structured literature review to identify the economic and health benefits and costs of measuring the Lp(a) concentration, potential barriers hindering the uptake of the measure, and potential solutions to address them. These findings were then discussed in an advisory board attended by experts and patient organisations., Results: It was found that if Lp(a) concentration is measured more widely today, patients, healthcare system and society would experience clinical and economic benefits even before specific Lp(a) lowering pharmacological treatments become available. Furthermore, a wider uptake of the Lp(a) measurement would support the development of epidemiological data., Conclusions: For Lp(a) measurement to be more widely used, key barriers which are hindering its uptake need to be addressed. These include i) the perception that the measure may have limited clinical value, ii) lack of awareness on Lp(a), iii) lack of data on the CV benefit of reducing Lp(a), iv) technical and clinical guidelines barriers, and v) healthcare system barriers. Scientific communities and industry should collaborate to address technical challenges and deficiencies in clinical guidelines. However, policy intervention will be crucial for national ASCVD plans to acknowledge the importance of Lp(a)., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
5. Lp(a): When and how to measure it.
- Author
-
Cegla J, France M, Marcovina SM, and Neely RDG
- Subjects
- Cardiovascular Diseases diagnosis, Humans, Risk Assessment, Risk Factors, Cardiovascular Diseases blood, Lipoprotein(a) blood
- Abstract
Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.
- Published
- 2021
- Full Text
- View/download PDF
6. The clinical and laboratory investigation of dysbetalipoproteinemia.
- Author
-
Boot CS, Luvai A, and Neely RDG
- Subjects
- Cholesterol analysis, Humans, Laboratories, Lipoproteins analysis, Lipoproteins, VLDL analysis, Triglycerides analysis, Hyperlipoproteinemia Type III diagnosis, Hyperlipoproteinemia Type III metabolism, Hyperlipoproteinemia Type III physiopathology
- Abstract
Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. The routine lipid profile cannot distinguish dysbetalipoproteinemia from other causes of mixed hyperlipidemia and so additional investigations are required for confident diagnosis or exclusion. A range of investigations that have been proposed as potential diagnostic tests are discussed in this review, but the definitive biochemical test for dysbetalipoproteinemia is widely considered to be beta quantification. Beta quantification can determine the presence of "β-VLDL" in the supernatant following ultracentrifugation and whether the VLDL cholesterol to triglyceride ratio is elevated. Both features are considered hallmarks of the disease. However, beta quantification and other specialist tests are not widely available and are not high-throughput tests that can practically be applied to all patients with mixed hyperlipidemia. Using apolipoprotein B (as a ratio either to total or non-HDL cholesterol or as part of a multi-step algorithm) as an initial test to select patients for further investigation is a promising approach. Several studies have demonstrated a high degree of diagnostic sensitivity and specificity using these approaches and apolipoprotein B is a relatively low-cost test that is widely available on high-throughput platforms. Genetic testing is also important in the diagnosis, but it should be noted that most individuals with an E
2 /2 genotype do not suffer from remnant hyperlipidemia and around 10% of familial dysbetalipoproteinemia cases are caused by rarer, autosomal dominant mutations in APOE that will only be detected if the gene is fully sequenced. Wider implementation of diagnostic pathways utilizing apo B could lead to more rational use of specialist investigations and more consistent detection of patients with dysbetalipoproteinemia. Without the application of a consistent evidence-based approach to identifying dysbetalipoproteinemia, many cases are likely to remain undiagnosed.- Published
- 2020
- Full Text
- View/download PDF
7. Corrigendum to "HEART UK consensus statement on Lipoprotein(a): A call to action" [Atherosclerosis 291 (2019) 62-70].
- Author
-
Cegla J, Neely RDG, France M, Ferns G, Byrne CD, Halcox J, Datta D, Capps N, Shoulders C, Qureshi N, Rees A, Main L, Cramb R, Viljoen A, Payne J, and Soran H
- Published
- 2020
- Full Text
- View/download PDF
8. HEART UK consensus statement on Lipoprotein(a): A call to action.
- Author
-
Cegla J, Neely RDG, France M, Ferns G, Byrne CD, Halcox J, Datta D, Capps N, Shoulders C, Qureshi N, Rees A, Main L, Cramb R, Viljoen A, Payne J, and Soran H
- Subjects
- Biomarkers blood, Blood Component Removal, Cardiovascular Diseases epidemiology, Cardiovascular Diseases prevention & control, Clinical Decision-Making, Consensus, Down-Regulation, Dyslipidemias diagnosis, Dyslipidemias epidemiology, Dyslipidemias therapy, Humans, Hypolipidemic Agents therapeutic use, Risk Assessment, Risk Factors, Dyslipidemias blood, Lipoprotein(a) blood
- Abstract
Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200 nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100 mg/dl (2.5 mmol/l) and 3) consideration of lipoprotein apheresis., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
9. Evaluation of the Non-HDL Cholesterol to Apolipoprotein B Ratio as a Screening Test for Dysbetalipoproteinemia.
- Author
-
Boot CS, Middling E, Allen J, and Neely RDG
- Subjects
- Area Under Curve, Female, Humans, Male, Nephelometry and Turbidimetry, ROC Curve, Retrospective Studies, Sex Factors, Ultracentrifugation, Apolipoproteins B blood, Cholesterol blood, Hyperlipoproteinemia Type III diagnosis, Lipoproteins, VLDL blood, Triglycerides blood
- Abstract
Background: Familial dysbetalipoproteinemia is associated with the accumulation of remnant lipoproteins and premature cardiovascular disease. Identification of dysbetalipoproteinemia is important because family members may be affected. Diagnostic testing involves demonstration of β-lipoprotein in the VLDL fraction or characterization of apo E
3 . These investigations are complex and relatively expensive. The ratios of apo B to total cholesterol and triglycerides have been proposed as screening tests. However, the ratio of non-HDL cholesterol to apo B (NHDLC/apoB) could offer improved performance as the confounding effect of variations in HDL cholesterol is removed., Methods: We evaluated NHDLC/apoB as a screening test for dysbetalipoproteinemia, using β-quantification analysis as a reference standard. Data from 1637 patients referred over a 16-year period for β quantification were reviewed retrospectively. In 63 patients, diagnostic criteria for dysbetalipoproteinemia (VLDL cholesterol/triglyceride ratio ≥0.69 and presence of β-VLDL) were fulfilled, and 1574 patients had dysbetalipoproteinemia excluded., Results: Mean NHDLC/apoB in patients with dysbetalipoproteinemia was 7.3 mmol/g (SD, 1.5 mmol/g) and with dysbetalipoproteinemia excluded was 4.0 mmol/g (SD, 0.5 mmol/g). The optimum cutoff of >4.91 mmol/g achieved a diagnostic sensitivity of 96.8% (95% CI, 89.0-99.6) and specificity of 95.0% (95% CI, 93.8-96.0). NHDLC/apoB offered improved performance compared to total cholesterol/apoB [diagnostic sensitivity 92.1% (95% CI, 82.4-97.4) and specificity 94.5% (95% CI, 93.2-95.6) with a cutoff of >6.55 mmol/g]. NHDL/apoB reference ranges were not sex-dependent, although there was a significant difference between men and women for total cholesterol/apoB., Conclusions: NHDLC/apoB offers a simple first-line test for dysbetalipoproteinemia in selecting patients with mixed hyperlipidemia for more complex investigations., (© 2018 American Association for Clinical Chemistry.)- Published
- 2019
- Full Text
- View/download PDF
10. Hematopoiesis Shows Closer Correlation with Calculated Free Testosterone in Men than Total Testosterone.
- Author
-
Woods DR, Hill NE, Neely RDG, Talks KL, Heggie A, and Quinton R
- Published
- 2017
- Full Text
- View/download PDF
11. Phaeochromocytoma and ACTH-dependent cushing's syndrome: tumour crf secretion can mimic pituitary cushing's disease.
- Author
-
Lois KB, Santhakumar A, Vaikkakara S, Mathew S, Long A, Johnson SJ, Peaston R, Neely RDG, Richardson DL, Graham J, Lennard TWJ, Bliss R, Miller M, Ball SG, Pearce SHS, Woods DR, and Quinton R
- Abstract
Introduction: 10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only five cases in the literature hitherto. However, such cases may be classified as 'ectopic ACTH' due to incomplete verification., Clinical Cases: We describe three patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom biochemical cure was achieved following unilateral adrenalectomy. Although unable to access a validated CRF assay within the timeframe for sample storage, we nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining (positive for CRF; negative for ACTH), supported in one case by pre-operative inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both cases were characterized by rapid postoperative wean off glucocorticoids, presumed to reflect the pituitary stimulatory-effect of CRF outweighing central negative feedback inhibition by hypercortisolaemia. By contrast, the tumour excised in a third case exhibited positive immunostaining for ACTH - negative for CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took significantly longer., Discussion: Ectopic CRF production is biochemically indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy. CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin some cases of cardiovascular collapse postadrenalectomy through acute hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous reports, we were unable to identify somatic DNA defects associated with either ACTH or CRF secretion., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.